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Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial (CIRCA-19 RCT)

Primary Purpose

Covid19, Acute Respiratory Distress Syndrome

Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
UC-MSCs
Placebo
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age of ≥18 years
  • Laboratory-confirmed SARS-CoV-2 infection during the current admission
  • On invasive, non-invasive mechanical ventilation (NIV) (PEEP ≥5 cmH20) or high-flow nasal canula (HFNC) oxygen therapy (minimum total flow rate of 40 lpm)
  • ARDS (onset <96h) as per the international consensus definition (P/F ratio < 300 with PEEP ≥5cm H20 or on HFNC), not due primarily to cardiac causes.

Exclusion Criteria:

  • No consent/inability to obtain consent
  • Rockwood Clinical Frailty Score > 4
  • Moribund patient not expected to survive 24 hours
  • Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  • Currently receiving extracorporeal life support
  • Pregnant or lactating
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Moderate to severe chronic liver disease (Childs-Pugh Score > 12)
  • Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen
  • Documented deep venous thrombosis or pulmonary embolism within the preceding 3 months
  • Inability/contra-indications to receiving local standard of care thromboprophylaxis
  • Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
  • Known HIV, Hep B/C positive, or active tuberculosis
  • Multisystem shock (SOFA score change from baseline of >2 in >2 systems)
  • Patient, surrogate, or physician not committed to full support including intubation (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)

Sites / Locations

  • Lakeridge HealthRecruiting
  • The Ottawa HospitalRecruiting
  • St. Michael's Hospital
  • Centre Hospitalier de l'Université de Montréal

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MSCs Arm

Placebo Arm

Arm Description

3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)

3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)

Outcomes

Primary Outcome Measures

Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28

Secondary Outcome Measures

Biomarkers of systemic inflammatory response
Interleukin levels change from Baseline to 24 hours after each MSC infusion
Biomarkers of endothelial function
Angiopoietin levels change from Baseline to 24 hours after each MSC infusion
ICU mortality
Number of deaths at day 28

Full Information

First Posted
April 27, 2021
Last Updated
May 4, 2021
Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT04865107
Brief Title
Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial
Acronym
CIRCA-19 RCT
Official Title
Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 27, 2021 (Actual)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
April 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 2 multicenter randomized (2:1), placebo-controlled trial to evaluate early signs of efficacy of allogeneic, umbilical cord-derived (UC) mesenchymal stromal cells (MSCs) in patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). Randomized participants (N=54) will receive 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) or blinded placebo. The MSC product will be provided as 2.5 million cells/ml suspended in PlasmaLyte A containing 5% Human Albumin. The appearance-matched placebo product contains the same excipients, PlasmaLyte A and 5% Human Albumin, as the UC-MSCs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Acute Respiratory Distress Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized (2:1) placebo-controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MSCs Arm
Arm Type
Experimental
Arm Description
3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
Intervention Type
Biological
Intervention Name(s)
UC-MSCs
Intervention Description
3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
PlasmaLyte A and 5% Human Albumin
Primary Outcome Measure Information:
Title
Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Biomarkers of systemic inflammatory response
Description
Interleukin levels change from Baseline to 24 hours after each MSC infusion
Time Frame
Change from Baseline to 24 hours after each MSC infusion
Title
Biomarkers of endothelial function
Description
Angiopoietin levels change from Baseline to 24 hours after each MSC infusion
Time Frame
Change from Baseline to 24 hours after each MSC infusion
Title
ICU mortality
Description
Number of deaths at day 28
Time Frame
Day 28
Other Pre-specified Outcome Measures:
Title
Safety events (SAEs, AEs)
Description
allergic reactions, infusion related reactions, and venous and arterial thrombotic events
Time Frame
At time of infusion until one year post-infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age of ≥18 years Laboratory-confirmed SARS-CoV-2 infection during the current admission On invasive, non-invasive mechanical ventilation (NIV) (PEEP ≥5 cmH20) or high-flow nasal canula (HFNC) oxygen therapy (minimum total flow rate of 40 lpm) ARDS (onset <96h) as per the international consensus definition (P/F ratio < 300 with PEEP ≥5cm H20 or on HFNC), not due primarily to cardiac causes. Exclusion Criteria: No consent/inability to obtain consent Rockwood Clinical Frailty Score > 4 Moribund patient not expected to survive 24 hours Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50% Currently receiving extracorporeal life support Pregnant or lactating Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial Moderate to severe chronic liver disease (Childs-Pugh Score > 12) Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen Documented deep venous thrombosis or pulmonary embolism within the preceding 3 months Inability/contra-indications to receiving local standard of care thromboprophylaxis Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months) Known HIV, Hep B/C positive, or active tuberculosis Multisystem shock (SOFA score change from baseline of >2 in >2 systems) Patient, surrogate, or physician not committed to full support including intubation (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Duncan J Stewart, MD
Phone
613-798-5555
Ext
7917
Email
djstewart@ohri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Duncan J Stewart, MD
Organizational Affiliation
The Ottawa Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lakeridge Health
City
Oshawa
State/Province
Ontario
ZIP/Postal Code
ON L1G 2B9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karim Soliman, MD
Email
ksoliman@lh.ca
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Duncan J Stewart, MD
Phone
+1 613-737-8899
Ext
75083
Email
djstewart@toh.ca
First Name & Middle Initial & Last Name & Degree
Shane English, MD
First Name & Middle Initial & Last Name & Degree
Dean Fergusson, PhD
First Name & Middle Initial & Last Name & Degree
Manoj Lalu, MD
First Name & Middle Initial & Last Name & Degree
Bernard Thebaud, MD
First Name & Middle Initial & Last Name & Degree
David Courtman, PhD
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia Dos Santos, MD
Email
Claudia.DosSantos@unityhealth.to
First Name & Middle Initial & Last Name & Degree
Kim Connelly, MD
Facility Name
Centre Hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 3E4
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michaël Chassé, MD
Email
michael.chasse@umontreal.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial

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